Inflammatory Bowel Disease
The inflammatory bowel diseases (IBD) are a group of chronic and debilitating condition which affect the gastrointestinal tract (GIT). The two main forms of IBD, are Crohn's disease (CD) and Ulcerative Colitis (UC). CD can affect any part of the GIT whereas UC affects the distal colon and rectum. The causes of IBD are not clearly understood, but are likely to involve a failure in the regulation of the immune response to normal intestinal bacteria and other microbial flora. As part of the Wellcome Trust Case Control Consortium and the UK IBD Genetics Consortium (UKIBDGC, www.ibdresearch.co.uk), we have used genome-wide association scans to identify many susceptibility genes or loci for CD and UC. We are also members of the International IBD Genetics Consortium (IIBDGC, www.ibdgenetics.org), which has now identified more than 200 susceptibility loci for IBD. This work has provided novel insights into the pathogenesis of IBD.
Areas of research in my group include investigation of the role of rare genetics variants in IBD through whole exome sequencing; analysis of the functional significance of non-coding regions at IBD risk loci; and exploring the transcriptome of the human colon. Using RNA sequencing of intestinal biopsies from IBD patient volunteers and controls we are surveying gene expression and novel intestinal-specific transcripts at the 200+ genomic regions associated with IBD susceptibility. These data can provide valuable functional information to inform the identification of true causal mechanisms underlying the genetic susceptibility to IBD.
In some individuals Crohn’s disease affects the mouth causing cracked swollen lips and painful oral ulceration. This rare form is sometimes referred to as orofacial granulomatosis or OFG and can occur with or without concurrent intestinal CD. We are recruiting volunteers with both types of OFG to investigate its genetic causes to see if they overlap with the genetic risk factors for the intestinal form of Crohn’s disease. We are also exploring whether microbial changes in the saliva of OFG patients are associated with disease or the onset of intestinal CD.